Bordetella pertussis is the primary causative agent of pertussis, or whooping cough, an acute infection of the respiratory tract. Pertussis occurs worldwide and is most severe when it infects unimmunized infants. Currently available vaccines (whole cell and partially purified acellular) are believed to have approximately 80-90% efficacy in the first few years after immunization. Effective immunization declines, in the case of whole cell vaccines, to almost no efficacy by 12 years postimmunization. The duration of protection provided by the acellular vaccine is unknown. The currently available vaccines are accompanied by a number of adverse reactions, some of which are severe or life-threatening. These severe reactions can include high fever, seizures, a shock-like hypo responsive state, encephalopathy and severe allergic reactions. In addition, individuals completely immunized with these vaccines can still develop pertussis. A purified component vaccine specific to the pertussis holotoxin would be useful for developing specific immunity to B. pertussis while minimizing potential adverse side effects caused by the currently available complex whole-cell or partially purified acellular vaccines.
One of the limitations of a purified component B. Pertussis vaccine is the time and expense involved in the growth and processing of large fermentor volumes of B. pertussis required to obtain sufficient amounts of pertussis holotoxin (PT) or mutated forms of the toxin protein, known as cross reactive materials or CRMs. Several investigators have attempted to overcome this limitation by over expression of PT using either homologous expression systems in B. pertussis , or in closely related B. parapertussis or B. bronchiseptica species (Lee, C. K. et al., Infect. Immun. 57:1413-1418 (1989)), or by utilizing heterologous expression systems such as E. coli or B. subtilis (Burnette, W. N. et al., Bio/Technology 699-705 (1988); Locht, C. and J. M. Keith, Science 232:1258-1264 (1986); Nicosia, A., et al., Proc. Natl. Acad. Sci. USA 83:4631 (1986)). Unfortunately, these efforts have failed to provide any system capable of consistently yielding amounts of PT holotoxin significantly greater than the amount obtained from cultures of wild type B. pertussis.